The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin ®) for the treatment of nausea and vomiting of pregnancy

Abstract

Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis(®), and has been on the Canadian market since 1979, currently under the brand name Diclectin(®). The efficacy of Diclegis(®)/Diclectin(®) has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis(®)/Diclectin(®) for the treatment of NVP to justify its use as first-line treatment for NVP.

Fig. 1

Chemical structure of Diclegis^®/Diclectin^® [10 mg doxylamine succinate/10 mg pyridoxine hydrochloride (HCl)]. a Doxylamine succinate is classified as an antihistamine. The chemical name for doxylamine succinate is ethanamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]-butanedioate (1:1) 2-[α-[2-(dimethylamino)ethoxy]-α-methylbenzyl] pyridine succinate (1:1). The empirical formula is C₁₇H₂₂N₂O · C₄H₆O₄ and the molecular mass is 388.46 g/mol. It is very soluble in water and alcohol, readily soluble in chloroform, and slightly soluble in ether and benzene. b Pyridoxine HCl is vitamin B₆. Its chemical name is 5-hydroxy-6-methyl-3,4-pyridine dimethanol hydrochloride. The empirical formula C₈H₁₁NO₃ · HCl and molecular mass is 205.64 g/mol. Pyridoxine HCl is readily soluble in water, slightly soluble in alcohol, and insoluble in ether